6 research outputs found

    Proper orthogonal decomposition of thermally-induced flow structure in an enclosure with alternately active localized heat sources.

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    The paper presents the structure of buoyancy-driven flow occurring in an enclosure with two alternately active discrete heat sources. For the analysis of the mixing of the fluid layer and its effect on heat transfer process, the flow information has been presented both in time and spectral domain. The inherent dynamics is also studied using the proper orthogonal decomposition (POD). POD technique is used here to assess the energy content in the different modes and the related coherent structures of flow considering different Rayleigh numbers (Ra = 103–106), switching frequencies (Z 1 with Z = 0.1–0.8) and air as working fluid of Prandtl number (Pr) of 0.71. The results reveal nonlinear characteristics of hydrodynamics and heat transfer at higher Ra for low frequency. Here, POD helps understanding the flow dynamics from information about the coherent structures of different energy modes

    NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1.

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    The NF-κB pathway is central to the regulation of inflammation. Here, we demonstrate that the low-output nitric oxide (NO) synthase 1 (NOS1 or nNOS) plays a critical role in the inflammatory response by promoting the activity of NF-κB. Specifically, NOS1-derived NO production in macrophages leads to proteolysis of suppressor of cytokine signaling 1 (SOCS1), alleviating its repression of NF-κB transcriptional activity. As a result, NOS1(-/-) mice demonstrate reduced cytokine production, lung injury, and mortality when subjected to two different models of sepsis. Isolated NOS1(-/-) macrophages demonstrate similar defects in proinflammatory transcription on challenge with Gram-negative bacterial LPS. Consistently, we found that activated NOS1(-/-) macrophages contain increased SOCS1 protein and decreased levels of p65 protein compared with wild-type cells. NOS1-dependent S-nitrosation of SOCS1 impairs its binding to p65 and targets SOCS1 for proteolysis. Treatment of NOS1(-/-) cells with exogenous NO rescues both SOCS1 degradation and stabilization of p65 protein. Point mutation analysis demonstrated that both Cys147 and Cys179 on SOCS1 are required for its NO-dependent degradation. These findings demonstrate a fundamental role for NOS1-derived NO in regulating TLR4-mediated inflammatory gene transcription, as well as the intensity and duration of the resulting host immune response

    Self-compassion, metabolic control and health status in individuals with type 2 diabetes: a UK observational study.

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    Aims: Self-compassion is a modifiable characteristic, linked with psychological well being and intrinsic motivation to engage in positive health behaviours. We aimed to explore levels of self-compassion in individuals with type 2 diabetes (T2DM) and their association with levels of depression, diabetes-related distress and glycaemic control. Methods: A cross-sectional study in 176 patients with T2DM in Leicester, UK, using three self-report questionnaires: the Self Compassion Scale (SCS); Patient Health Questionnaire (PHQ-9), and Diabetes Distress Scale (DDS-17). Demographic data, medical history and blood samples were collected. Results: Majority of participants were male (n=120, 68.2%), with median [IQR] age and HbA1 c of 66 [60, 71] years and 7.3 [6.7, 8.0] %, respectively. Multivariable analysis adjusting for age, gender, ethnicity and diabetes duration revealed significant association of all three scores with HbA1 c : per one standard deviation increase of each score, a -0.16% reduction in HbA1 c for SCS (p=0.027), 0.21% increase for PHQ-9 (p=0.012) and 0.33% increase for DDS-17 (p<0.001). Conclusions: Higher levels of self-compassion and lower levels of depressive symptoms were associated with significantly better long-term diabetes control. These results reinforce the importance of emphasis on psychological parameters, including self-compassion, in the multi-disciplinary management of T2DM. We identify this as a potential area for intervention in UK practice

    The rationale and design of a cross-sectional study to investigate and describe the Chronotype of Patients with Type 2 Diabetes and the Effect on Glycaemic Control: The CODEC study

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    Introduction A person’s chronotype is their entrained preference for sleep time within the 24-hour clock. It is described by the well-known concept of the ‘lark’ (early riser) and ‘owl’ (late sleeper). Evidence suggests that the ‘owl’ is metabolically disadvantaged due to the standard organisation of our society which favours the ‘lark’ and places physiological stresses on this chronotype. The aim of this study is to explore cardiometabolic health between the lark and owl in a population with an established metabolic condition - Type 2 Diabetes. Methods This cross-sectional, multi-site study aims to recruit 2247 participants from both secondary and primary care settings. The primary objective is to compare glycaemic control between late and early chronotypes. Secondary objectives include determining if late-chronotype is associated with poorer cardiometabolic health and other lifestyle factors, including well-being, compared to early-chronotype; describing the prevalence of the five different chronotypes in this cohort and examining the trends in glycaemic control, cardiometabolic health, well-being and lifestyle factors across chronotype. Analysis The primary outcome (HbA1c), linear regression analysis will compare HbA1c between early and late chronotypes, with and without adjustment for confounding variables. Chronotype will be modelled as a categorical variable with all five levels (from extreme-morning to extremelate type), and as a continuous variable to calculate p for trend across the five categories. A number of models will be created; unadjusted through to adjusted with age, sex, ethnicity, BMI, duration of diabetes, family history of diabetes, current medication and dietary habits. All secondary outcomes will be analysed using the same method. Ethics Ethical approval from the West Midlands - Black Country Research Ethics Committee (16/WM/0457). Dissemination The results will be disseminated through publication in peer reviewed medical journal, relevant medical/health conferences and a summary report sent to patients. Registration details Registered on clinicaltrials.gov NCT02973412 (23.11.20116

    The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: the SEESAW randomised, double-blind, placebo-controlled trial

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    Aim To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity. Materials and Methods In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.0% [42-86 mmol/mol]) and body mass index of 25 kg/m2 or higher were randomized to (a) placebo only, (b) placebo plus diet, (c) empagliflozin only or (d) empagliflozin plus diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360 kcal/day). The primary outcome was change in postprandial circulating total peptide-YY (PYY) during a 3-hour mixed-meal tolerance test from baseline to 24 weeks. Postprandial total glucagon-like peptide-1 (GLP-1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance. Results The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: −8.6 [−28.6 to 11.4], 13.4 [−6.1 to 33.0] and 1.0 [−18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions. Conclusions In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy.</p
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